Gliederung

Objective: Deficient sensorimotor gating induced by dopamine receptor agonists is used as an endophenotype for certain neuropsychiatric disorders such as Tourette's syndrome, schizophrenia, and attention deficit disorders. One operational measure of sensorimotor gating is prepulse inhibition (PPI) of the acoustic startle response (ASR). Here, we investigated whether deep brain stimulation (DBS) of the rat entopeduncular nucleus (EPN), the equivalent to the human globus pallidus internus (GPi), would improve PPI-deficits induced by the dopamine receptor agonist apomorphine. Additionally, we investigated the effects of DBS on apomorphine-induced stereotypies.

Methods: Bipolar electrodes were stereotactically implanted bilaterally into the EPN of Sprague Dawley rats (n=9). After one week of recovery, the individual threshold for side effects was determined in each rat. Thereafter rats were stimulated (130 Hz, 80Âµs pulse width) or sham-stimulated for a period of five days. At the end of each period, rats were tested during stimulation for prepulse inhibition (PPI) of startle, and subsequently for stereotypies after subcutaneous injection of apomorphine (1.0 and 0.5 mg/kg, respectively). Rats injected with a vehicle (saline) were used as controls.

Conclusions: This work indicates an important role of the EPN in the modulation of dopamine agonist-induced deficient sensorimotor gating. DBS of the EPN in rats may serve as a model to further investigate the mechanisms of DBS in neuropsychiatric disorders with deficient sensorimotor gating.